Secondary Spread Research Articles

Synthesis of a novel nanobioconjugate for targeted photodynamic therapy of colon cancer enhanced with cannabidiol.

Photodynamic therapy (PDT) is a promising primary treatment option for colorectal cancer (CRC), however CRC is accelerated by resilient CRC stem-like cells, which decrease its efficacy. In recent years, researchers have shown an emerging interest in the anticancer stem cell effects of cannabidiol (CBD). This study developed a targeted nanobioconjugate for specific ZnPcS4 photosensitizer intracellular accumulation within in vitro cultured human CRC cells (CaCo-2) for enhanced PDT primary treatment, as well as limited its secondary spread by combining this treatment with CBD. The final nanobioconjugate (FNBC) was successfully synthesized and characterized using various methods. The cytotoxicity of the FNBC and CBD were tested on CRC cells using laser irradiation at 673 nm with a fluency of 10 J/cm2. 24 h post treatment, morphological changes were assessed via microscopy, cell viability was measured using Annexin V-FITC and cellular nuclear DNA was visualized under fluorescent microscopy, following Hoechst staining. FNBC and CBD combinative treatment induced the most significant photodamage, leaving a staggering 6%*** viable cells. Overall, through active targeting of CRC cells using the FNBC, the enhanced PDT primary treatment of CRC was achieved, and the combinative treatment with CBD noted significant limitations on its secondary spread.

Dynamics of bacterial blight disease in resistant and susceptible rice varieties

Bacterial blight (X. oryzae pv. oryzae) is a serious disease in rice across the world. To better control the disease, it is important to understand its epidemiology and how key aspects of this (e.g. infection efficiency, and spatial spread) change according to environment (e.g. local site conditions and season), management, and in particular, variety resistance. To explore this, we analysed data on the disease progress on resistant and susceptible varieties of rice grown at four sites in the Philippines across five seasons using a combination of mechanistic modelling and statistical analysis. Disease incidence was generally lower in the resistant variety. However, we found no evidence that the primary infection efficiency was lower in resistant varieties, suggesting that differences were largely due to reduced secondary spread. Despite secondary spread being attributed to splash dispersal which is exacerbated by wind and rain, the wetter sites of Pila and Victoria in south Luzon tended to have lower infection rates than the drier sites in central Luzon. Likewise, we found spread in the dry season can be substantial and should therefore not be ignored. In fact, we found site to be a greater determinant of the number of infection attempts suggesting that other environmental and management factors had greater effect on the disease than climate. Primary infection was characterised by spatially-random observations of disease incidence. As the season progressed, we observed an emerging short-range (1.6 m–4 m) spatial structure suggesting secondary spread was predominantly short-range, particularly where the resistant variety was grown.

Enhancement of Conventional and Photodynamic Therapy for Treatment of Cervical Cancer with Cannabidiol.

Cervical cancer (CC) is the fourth most diagnosed cancer in women worldwide. Conventional treatments include surgery, chemo- and radiotherapy, however these are invasive and may cause severe side effects. Furthermore, approximately 70% of late-stage CC patients experience metastasis, due to treatment resistance and limitations. Thus, there is a dire need to investigate alternative therapeutic combination therapies. Photodynamic therapy (PDT) is an alternative CC treatment modality that has been clinically proven to treat primary CC, as well as to limit secondary metastasis. Since PDT is a non-invasive localized treatment, with fewer side effects and lessened resistance to dose repeats, it is considered far more advantageous. However, more clinical trials are required to refine its delivery and dosing, as well as improve its ability to activate specific immune responses to eradicate secondary CC spread. Cannabidiol (CBD) isolates have been shown to exert in vitro CC anticancer effects, causing apoptosis post treatment, as well as inducing specific immune responses, which obstruct tumor invasion and angiogenesis, and so hinder CC metastatic spread. This review paper discusses the current conventional and alternative PDT treatment modalities for CC, as well as their limitations over the last 10 years. It has a particular focus on the combinative administration of CBD with these treatments in order to prevent CC secondary migration and so possibly encourage future research studies to focus on this synergistic effect to eradicate CC.

Evaluating the timing of insecticide application to manage barley yellow dwarf virus and yield in winter barley

Barley yellow dwarf virus (BYDV) is an important viral disease of grain crops worldwide and a major cause of yield loss. The risk periods for BYDV infection coincide with milder temperature that prolongs aphid flight and facilitates viral transmission through primary and secondary aphid movement in the crop. Secondary aphid movement is associated with greater BYDV spread in winter cereals. A critical component of BYDV management is therefore delaying sowing of winter cereals and correctly timing insecticide application to maximise crop protection. Previous research in Ireland considered insecticide timing in early (September) and late (October onwards) sown cereals. Early research did not consider action thresholds around temperature, aphid flight and risk of secondary spread. This research set out to understand the optimal timing of insecticide application in October sown winter barley to reduce BYDV infection and yield impact. A critical temperature of 3°C was used as a threshold for aphid development that leads to movement and BYDV spread, and insecticide treatments were applied to the crop at predictable intervals in relation to temperature. Results show that BYDV symptoms and yield are affected by spray time, location and year, although only significant with regard to the reduction of BYDV symptoms. For both BYDV symptoms and yield, there was a significant difference between untreated (control) plots and “early” and “late” applications of insecticide, again more notable for BYDV symptoms than yield. This work indicates the value of optimising a single insecticide spray for control of October sown cereals and supports decision-making in the management of cereal crops.

Recent concepts in fungal involvement in skin and soft tissue infections.

The aim of this review is to provide an overview of the most frequent and emerging deep cutaneous fungal infections following either primary inoculation or secondary spread after haematogenous seeding in disseminated infections in different geographical areas. Fungal skin and soft tissue infections (SSTIs) encompass a variety of pathological conditions based on the site of the infection, route of acquisition of the pathogen, epidemiological setting and the virulence of the fungus in relation to the host. The approach to a patient suspected of having a fungal SSTI is complex and usually poses a major diagnostic challenge. The treatment approach should include attempts at immune reconstitution, targeted antifungal therapy and/or aggressive surgical debridement. Fungal SSTIs can be an important cause of morbidity and mortality in both immunocompromised and immunocompetent patients and are being reported with increasing frequency worldwide.

Targeted next‐generation sequencing of environmental DNA improves detection of invasive European green crab (Carcinus maenas)

AbstractIn the northeast Pacific Ocean, there is high interest in developing eDNA‐based survey methods to aid management of invasive populations of European green crab (Carcinus maenas). Expected benefits are improved sensitivity for early detection of secondary spread and to assess the outcome of eradication efforts. A new eDNA‐based approach we term “targeted next‐generation sequencing (tNGS)” is introduced here and shown to improve detection relative to qPCR at sites with lower green crab CPUE values measured by trapping. DNA standards (gBlock) with starting molecule copies that were 10 to 100 times lower than the qPCR limit of detection returned significant numbers of sequencing reads, which in our field assessments translated to a 7%–10% increase in detection probability from tNGS relative to qPCR at sites with lower CPUE. We also found the number of sequencing reads from tNGS was significantly correlated with green crab CPUE whereas Ct values from qPCR were not. When sources of variation were partitioned for each assay, we found the difference between mean within‐site and mean between‐site variation was much larger and had non‐overlapping confidence intervals for tNGS relative to qPCR, suggesting the former may offer more power for detecting spatial variation in eDNA availability. Results presented here indicate this approach is suitable for species of known low abundances where a positive detection has high economic or environmental consequences, or for labs doing eDNA surveys for whom NGS‐based workflows are operationally more efficient than qPCR given its upward scalability. Any species with an existing qPCR assay can be easily tested with a tNGS assay using the approach presented here. We conclude with a discussion on the fitness for purpose of tNGS vs. qPCR for various applications and on how to best apply molecular surveys in management programs.

Introduction, spread, and impacts of invasive alien mammal species in Europe.

Biological invasions have emerged as one of the main drivers of biodiversity change and decline, and numbers of species classed as alien in parts of their ranges are rapidly rising. The European Union established a dedicated regulation to limit the impacts of invasive alien species (IAS), which is focused on the species on a Union List of IAS of particular concern. However, no previous study has specifically addressed the ecology of invasive alien mammals included on the Union List.We performed a systematic review of published literature on these species. We retrieved 262 publications dealing with 16 species, and we complemented these with the most up‐to‐date information extracted from global databases on IAS.We show that most of the study species reached Europe as pets and then escaped from captivity or were intentionally released. On average each year in the period 1981–2020, 1.2 species were recorded for the first time as aliens in European countries, and most species are still expanding their alien ranges by colonising neighbouring territories. France is the most invaded nation, followed by Germany, Italy, and the Russian Federation, and the muskrat Ondatra zibethicus, the American mink Neovison vison, and the raccoon dog Nyctereutes procyonoides are the most widespread species, having invaded at least 27 countries each. Invasive mammals of European Union concern are threatening native biodiversity and human well‐being: worryingly, 81% of the 16 study species are implicated in the epidemiological cycle of zoonotic pathogens.Containing secondary spread to further countries is of paramount importance to avoid the establishment of new populations of invasive mammals and the related impacts on native communities, ecosystem services, and human health.We present a compendium on the ecology and impacts of invasive mammals of European Union concern. It can be used to assist environmental policies, identify and subsequently fill knowledge gaps, and inform stakeholders.

Several decades of two invasive fish species (Perccottus glenii, Pseudorasbora parva) of European concern in Lithuanian inland waters; from first appearance to current state

Following their first appearance, the invasive fishes Pseudorasbora parva and Perccottus glenii have been in Lithuania for several decades. However, until recently, information relating to their distribution and secondary spread was limited. For this reason, suitable habitats for these fish species were surveyed for their presence across the entire country. Additionally, all previously reported records on the presence of these species were summarized. Results revealed P. glenii to be widely distributed within the country with abundant populations in habitats suitable for the species. The recent distribution of P. parva is restricted to only a few water bodies. It was shown that both species are associated with human mediated transfer, while no natural dispersal of these invasive species was observed. The results of this study suggest that the invasion of Lithuanian inland waters by P. parva and P. glenii is still ongoing, and their occurrence in numerous water bodies, which are still devoid of these species, now seems probable. Demonstrated vectors of P. parva and P. glenii introductions in Lithuania highlight the importance of controlling and screening human activities related to aquaculture, recreational angling and the ornamental fish trade in order to restrict further P. glenii and P. parva expansion in this region.

The role of marinas in the establishment and spread of non-indigenous species in Baltic Sea fouling communities

The study included the sampling of 12 marinas across six areas of the Baltic Sea with settlement plates and scraping of submerged structures to assess the role of marinas in the spread of non-indigenous species (NIS) via biofouling. 15 NIS were detected in the marinas and secondary spread of previously introduced NIS was detected in five out of six sea areas. Salinity and sea area significantly affected the composition of the fouling assemblages. Settlement plates appeared as the more efficient sampling method over scraping, while the seasonal analyses revealed that the monitoring effort should span over the summer and early autumn in the south-eastern, central, and northern Baltic Sea. The present findings indicate that marinas contribute to the spread of non-indigenous fouling organisms, and there is an increasing demand for the monitoring of marinas and stricter regulations regarding the biofouling management of leisure boats in the Baltic Sea.

Attention-Deficit/Hyperactivity Disorder as a Risk Factor for COVID-19 Infection

Objective: To postulate that ADHD is a potential risk factor for COVID-19 infection; to evaluate the COVID-19 risk factor on drug-treated ADHD subjects. Methods: A retrospective chart review was performed on ADHD subjects aged 6 to 18 years in Israel, who had undergone at least one COVID-19 test during the study period. Results: Of the 64,409 subjects included in the study, 6,207 (9.64%) had at least one positive COVID-19 test result, 13,300 (20.65%) were diagnosed with ADHD, and of whom 1,751 (13%) had purchased at least two ADHD medications 3 months prior to COVID-19 testing and were defined as being medically treated. Medically-treated ADHD subjects had a significantly lower likelihood to be infected with COVID-19 than untreated subjects. Conclusion: Untreated ADHD patients seem to constitute a risk group for COVID-19 infection. Drug treatment ameliorates risk of spreading COVID-19 infection within the pediatric population and secondary spread in the general population.

Non-Indigenous Species on Artificial Coastal Environments: Experimental Comparison between Aquaculture Farms and Recreational Marinas

Globally, there is growing concern regarding the effects of the increasing anthropogenic pressures in marine communities. Artificial structures such as marinas and aquaculture facilities serve as invasion hotspots; hence, monitoring fouling communities on these structures can be valuable for detecting new invasions. In the current study, 24 settlement PVC plates were deployed for three months to compare the recruitment ability of these two artificial environments along the south coast of the offshore island of Madeira (NE Atlantic). The results showed higher variations in the species richness between regions (SW vs. SE) than between artificial habitats (sea-cages vs. marinas), although the community composition differed. Cnidaria and Bryozoa were the most representative groups in the aquaculture systems, while Bryozoa and Chordata were in the marinas. A sum of 18 NIS was recorded for the study, accounting for between 21.88% and 54.84% of the total number of species in the aquaculture facilities and marinas, respectively. The higher NIS percentage from the marinas was even more explicit in the SE coast, where Cradoscrupocellaria bertholletii, Parasmittina alba, and Botrylloides niger distinctly dominated fouling populations. The results suggest that at least some particular NIS previously reported in the studied marinas successfully colonized sea-cages. Future assessments need to address the potential role of aquaculture facilities as drivers for the secondary spread of NIS. Additionally, two new records are considered for Madeira: Eudendrium capillare and Ericthonius punctatus.

Multicomponent Strategies to Prevent SARS-CoV-2 Transmission — Nine Overnight Youth Summer Camps, United States, June–August 2021

Most U.S. overnight youth camps did not operate during the summer of 2020 because of the COVID-19 pandemic* (1). Several that did operate demonstrated that multiple prevention strategies, including pre- and postarrival testing for SARS-CoV-2, the virus that causes COVID-19, masking, and physical distancing helped prevent the introduction and spread of COVID-19; in contrast, camps that relaxed prevention strategies, such as requiring a single prearrival test without subsequent testing, experienced outbreaks (2-4). The availability of COVID-19 vaccines for persons aged ≥12 years enabled implementation of an additional prevention strategy that was not available in summer 2020. This study assessed the number of COVID-19 cases and potential secondary spread among 7,173 staff members and campers from 50 states, 13 countries, and U.S. military overseas bases at nine independently operated U.S. summer youth camps affiliated with the same organization. The camps implemented multiple prevention strategies including vaccination, testing, podding (cohorting), masking, physical distancing, and hand hygiene during June-August 2021. Vaccination coverage was 93% among eligible persons aged ≥12 years.† All staff members (1,955) and campers (5,218) received site-specific, protocol-defined screening testing, which included prearrival testing and screening tests during the camp session (38,059 tests). Screening testing identified six confirmed COVID-19 cases (one in a staff member and five in campers) by reverse transcription-polymerase chain reaction (RT-PCR) testing (screening test positivity rate=0.02%). Three additional cases (in two staff members and one camper) were identified based on symptoms and were confirmed by RT-PCR testing. Testing for SARS-CoV-2, isolation, and quarantine in a population with high vaccination coverage resulted in no known secondary transmission of SARS-CoV-2 identified during camp. Implementation of multicomponent strategies is critical for prevention of COVID-19 outbreaks in congregate settings, including overnight youth camps.

Duplex kidney complicated with preoperative inferior nephroblastoma rupture in children: a case report and literature review

BackgroundWe admitted a child with a duplex kidney combined with preoperative rupture of nephroblastoma and used this case to discuss the clinical features and treatment of this disease.Case presentationWe retrospectively analyzed the clinical data of a 5-year-old girl with preoperative duplex kidney rupture combined with inferior nephroblastoma who was admitted to the Fourth Hospital of Baotou. In addition, we reviewed the relevant literature. The patient’s details were as follows: weight, 17 kg; height, 108 cm; and body surface area, 0.7 m2. Abdominal ultrasound for abdominal pain revealed the presence of a left-sided renal mass; enhanced abdominal computed tomography further confirmed it to be a left-sided duplex kidney measuring approximately 6 × 5 × 5 cm, with a rupture originating from the lower kidney. The PubMed database was searched from 2010 to 2020 for the terms “Wilms’ tumor” and “Duplex” and “Wilms’ tumor” and “Rupture.” The treatment plan was preoperative chemotherapy (vincristine/dactinomycin, VA regimen) + left kidney tumor radical surgery + postoperative chemotherapy (actinomycin-D/VCR/doxorubicin, AVD regimen). Postoperative pathology revealed an International Society of Pediatric Oncology intermediate-risk stage-3 nephroblastoma (mixed type) in the left kidney. Literature review was performed with 71 cases meeting the set criteria with an aim to analyze and summarize the clinical characteristics and treatment of patients with ruptured nephroblastoma and duplex kidney combined with nephroblastoma.ConclusionsTo our knowledge, no previous studies have reported preoperative duplex kidney combined with nephroblastoma rupture. In patients with this condition, preoperative chemotherapy is recommended when the vital signs are stable and tumor resection can be performed after the tumor has shrunk to prevent secondary spread. If the patient’s vital signs are unstable, emergency exploratory surgery is needed. If the nephroblastoma rupture is old and limited, surgery can be performed when the tumor size is small.

High Seedling Mortality of Scots Pine Caused by Heterobasidion annosum s.s.

This study provides new information on the infection biology and pathogenicity of an important root-rot fungus, Heterobasidion annosum sensu stricto (Fr.) Bref., through a detailed examination of the vegetative spread of clonal individuals and their capacity to produce fruiting bodies on young pine seedlings. The seedlings were planted in a clear-cutting area (c. 1.2 ha in size) after a pine generation that showed slight external symptoms of Heterobasidion root rot. The first dead seedlings were found five years after planting and during a nine-year monitoring period; nearly 600 seedlings were killed by H. annosum s.s. in 48 individual disease centers. Based on pairing tests of 482 isolates, 117 different H. annosum s.s. genotypes were identified. On average, 2.9 genotypes occurred in a single disease center. The extensive secondary spread of genotypes within root systems (up to 48 pine seedlings infected by the same genotype) resulted in annually expanding disease centers. In addition, more than half of the seedlings killed by H. annosum s.s. produced perennial fruiting bodies thus providing air-borne inoculum. The risk of spore infection should be taken into account in any type of cutting operation in young pine stands. Moreover, new control measures directed towards the secondary spread of H. annosum s.s. in pine regeneration are urgently needed in order to maintain the productivity of the pine forest on infested sites.

Can ‘On-Farm’ Seed Priming and Chitosan Seed Treatments Induce Host Defences in Winter Barley (Hordeum vulgare L.) under Field Conditions?

Enhancing host defences through induced resistance, disease tolerance, and/or escape, in combination with current disease management regimes may be a valuable strategy to reduce pesticide use. Since both ‘on-farm’ seed priming (OSP) and chitosan priming (CHP) have been reported to confer varying levels of host defence, this study sought to investigate their potential to deliver disease control as a strategy for sustainable management of foliar pathogens in winter barley. Field experiments were conducted to determine the effects of OSP and CHP at two different field sites using three different cultivars under fungicide/non-fungicide regimes. Overall, no evidence was found to suggest that CHP or OSP can induce effective resistance in temperate field conditions. However, these field trials enabled the identification of candidate traits to deliver disease tolerance (and escape) for the primary and secondary spread of powdery mildew, i.e., large canopies and rapid stem elongation respectively. Thus, these seed treatments may deliver disease tolerance and escape traits, but these benefits are dependent upon successful establishment and vigour first. The integration of seed treatments into sustainable crop protection may be better undertaken with spring crops or in semi-arid agriculture where the added vigour at emergence can help compensate for negative environmental interactions.

Early detection of marine invasive species following the deployment of an artificial reef: Integrating tools to assist the decision-making process

Early detection and rapid response plans are a set of principles to reduce the establishment, spread and impact of invasive species and it is a critical step in management in marine ecosystems. Two potentially invasive ascidians attached to the hull of a recently sunk fishing vessel were early detected in Patagonia. With the aim of assisting in the management decision-making process during the early steps of a rapid response, we conducted several analyses through different approaches. First, we identified the species through classic taxonomical and genetic analyses. Then, we evaluated the regional and international shipping connectivity to study potential donor regions and finally, we used species distribution models (SDMs) to predict the potential distribution of these species. The potentially invasive ascidians were identified as Styela clava and Styela plicata, and this is the first record for both species in the Nuevo gulf, Patagonia Argentina. Both species have a widespread distribution around the world with strong ecological and economic impacts documented. Shipping traffic analysis suggested that S. plicata could have arrived by secondary spread from regional ports, while the arrival of S. clava was likely to be associated with international shipping traffic. Furthermore, the SDM predicted that S. clava has suitable coastal areas along the entire Southwestern Atlantic shoreline, where it is currently absent. On the contrary, the SDM predicted that further southward spread of S. plicata is unlikely, being limited by the minimum annual temperature. We discussed the different approaches, tools, and expertise integrated in this work in the light of the decision-making process for the early detection of marine invasive species in the Southwestern Atlantic. Moreover, we call attention to the increased creation of artificial habitats through the intentional sinking of ships and the potential consequences of these actions in the conservation of marine ecosystems.

Native vs. non-indigenous macroalgae in Iceland: The state of knowledge

In the last decades, there has been an increase of macroalgal species appearing in new geographic regions. These new records are being linked to non-intentional global human-mediated transport. In Iceland three macroalgae species have been reported as non-indigenous. We updated the number of non-indigenous macroalgae to 8 species, 4 of which are potentially invasive. Pathways and vectors of each macroalga introduction are identified. The red algae group does not stand out in Iceland as in the nearest territories. The number of non-indigenous macroalgae will probably increase in the near future due to (1) secondary spread of species via shipping vector; (2) the growing trend of aquaculture in Norway, where surface currents will probably allow the spread of algae to Iceland; and (3) the increase of studies focusing on this matter. To address the problem, we suggest that local monitoring and mitigation programmes should be implemented across Iceland, and that regulatory and preventive measures for the maritime traffic vector should be developed.

Skin lymphomas (photogallery)

Skin lymphomas are a heterogeneous group of lymphoproliferative diseases characterized by clonal proliferation and primary accumulation of tumor lymphocytes in the skin with the possibility of secondary extracutaneous spread (lymph nodes, blood, spleen, lungs, liver). 65% of all skin lymphomas originate from mature T-cells, 25% from mature B-cells, 10% originate from natural killer cells (NK).

Neurophysiological phenotypes of pharmacoresistant temporal lobe epilepsy

Patients with a drug-resistant form of epilepsy can be treated by neurosurgery through the destruction or separation of the epileptic focus. If the results of clinical, neuro-imaging and neurophysiological methods are discordant, then the localization of the epileptogenic zone is performed based on the results of long-term invasive monitoring of the bioelectrical activity of the cortex and deep structures of the brain. The aim of this work was the retrospective analysis of the results of invasive monitoring of the bioelectrical activity of the brain to clarify the mechanisms of the formation of patterns of interictal and ictal activity in structural epilepsy. The study included 35 patients (18 men, 17 women) with drug-resistant temporal lobe epilepsy, who were treated at the Polenov Neurosurgical Institute. The examination included video-EEG monitoring, long-term invasive monitoring of bioelectrical activity of the cortex, and deep brain structures. The patients were divided into two groups according to the type of surgical treatment: 1) micro-surgical resection of the epileptic focus, including the zone of structural changes (24 patients); 2) stereotactic destruction of the amygdala-hippocampal complex (6 patients). The follow-up of the outcomes of the surgical treatment took place over 2-3 years. Depending on the results of the surgical treatment, the patients were divided into two groups: 1) patients with a favorable outcome (Engel 1–2) — 15 patients and 2) patients with no positive dynamics and a relatively poor outcome (Engel 3–4) — 15 patients. The results obtained showed that the patterns of interictal and ictal activity in their totality determine the neurophysiology, i.e the phenotype of temporal lobe epilepsy, reflecting the interference of pathogenetic and sanogenetic mechanisms. The localization of the epileptogenic zone should be based on the cumulative assessment of interictal and ictal activity. The presence of more than one focus of interictal activity, the secondary spread of epileptiform activity from the primary focus, are prognostically unfavorable factors.

Биоактивные покрытия на металлических сплавах и стимуляция восстановления кости после перелома

The survey of the literature data and authors’ research on molecular-cell mechanisms of the osteoinductive effect of calcium-phosphate compounds and their importance during fracture healing. The usage of titanium implants containing calcium-phosphate and hydroxyapatite covering leads to structural transformation of the bony tissue in the interstitial gap and activation of the reparative processes. This activities correlate with the changes in expression of morphogenetic and apoptotic factors in different stages of the reparative osteogenesis. Reparative effect of the calcium-phosphate compounds can be estimated as a sum of cambial activity CD44-reactive mesenchymal stem cells and secondary fracture spread – the apoptosis of the cells of bone regenerate. The interaction of these processes in each stage of bone healing provides bone morphogenetic proteins, vascular endothelial growth factor and transformative growth-factor-β. Current issues of the metal alloy with bioresorbable covering for the long bones healing are discussed.